Pancreas cancer treated with surgery alone has produced disappointing results including high rates of positive margins and rapid development of distant metastases

At the time of initiation of this study, adjuvant chemoradiation was widely considered the standard treatment following curative surgery (which has since become a point of controversy, as additional evidence has placed into question the need for radiation post-operatively [ESPAC-1])

Gemcitabine is known to be active in advanced pancreas cancer and is a powerful radiation sensitizer

Gemcitabine and oxaliplatin have been shown to have supra-additive effect in-vitro

This study was derived as an attempt to more adequately treat micrometastatic disease earlier in the treatment course

This is a Phase II study to look at the feasibility and effectiveness of treating completely resected pancreas cancer patients with 6 cycles of Gemcitabine/Oxaliplatin (GemOx) followed by concurrent gemcitabine and radiation (GemRT)

Materials and Methods

Multi-institutional prospective Phase II, single arm study

Post-operative patients were treated with 6 cycles of GemOx followed by a 4-week break, and then received GemRT

85% of patients completed all 6 cycles of chemotherapy and 76% completed GemRT

Of patients receiving radiation, 98% completed 50 Gy

1-year recurrence free survival 71%

2-year overall survival 74%

8 of 51 patients developed distant metastases prior to GemRT

Acute Grade 3/4 toxicity

GemOx – 29% hematologic, 16% gastrointestinal

2 Grade 4 neutropenia

GemRT – 19% neutropenia, 70% thrombocytopenia

2 Grade 4 (neutropenia and esophagitis)

Late Grade 3/4 toxicity – 2% paresthesia, 2% anemia

44% of tumors were in the pancreatic head

29% were confined to the pancreas with 64% invading duodenum or peripancreatic tissue

No treatment related deaths

Author's Conclusions

Adjuvant GemOx followed by GemRT is both feasible and well tolerated for treatment of completely resected adenocarcinoma of the pancreas

These data are encouraging with regards to both recurrence free and overall survival and warrants further exploration of adjuvant chemotherapy followed by chemoradiation

The presenter suggests that early initiation of chemotherapy prior to initiation of radiation may select out those patient who would develop distant metastases sooner, and thereby be less likely to benefit from local treatment i.e. radiation therapy

Clinical/Scientific Implications

These data demonstrate the tolerability of adjuvant chemotherapy followed by chemoradiation with a gemcitabine containing regimen for completely resected adenocarcinoma of the pancreas

This warrants further investigation in a randomized controlled study to demonstrate improved clinical efficacy of this regimen over either chemotherapy or chemoradiation alone using standard regimens